This unit, which overlaps both the Biological Psychiatry Branch and the Laboratory of Clinical Psychopharmacology, has conducted studies on both clinical and basic aspects of sleep for many years. This unit has made major attempts both to characterize the sleep disorder of depression, and to understand its mechanism, both from the point of view of neuropharmacological models and underlying circadian rhythms. Our findings suggest that muscarinic supersensitivity may be present in patients with primary affective illness both in remission and when ill. Our data suggest that patients with primary affective illness demonstrate muscarinic supersensitivity as measured by pupillary constriction to pilocarpine, and by the Cholinergic REM Induction Test. The unit has also made major investigations on neuroendocrine relationships to sleep-wakefulness and to certain specific sleep disorders, including insomnia. Our studies on human learning and memory suggest that cholinergic agonists facilitate specific types of cognition, whereas blockade of catecholamine neurotransmission inhibits cognitive performance.